This study systematically characterized the chemical composition of Yuanhu Zhitong Oral Liquid (YZOL) and elucidated its therapeutic mechanism in primary dysmenorrhea (PD). Using UPLC-Q-TOF-MS/MS, a total of 100 constituents were preliminarily identified in YZOL, predominantly isoquinoline alkaloids and coumarins. A rat model of PD was established by combined administration of estradiol benzoate and oxytocin, and the pharmacological effects of YZOL were comprehensively evaluated through behavioral assessment, quantification of dysmenorrhea-related mediators, and histopathological examination. The results demonstrated that YZOL significantly reduced writhing frequency and prolonged writhing latency in PD rats (P < 0.05). Specifically, medium- and high-dose YZOL markedly decreased the PGF_2α/PGE₂ ratio (P < 0.05), while all dose groups significantly reduced the TXB₂/6-keto-PGF_1α ratio (P < 0.05). Consistently, YZOL treatment markedly ameliorated uterine histopathological damage, with the high-dose group exhibiting tissue morphology closest to normal. Transcriptomic profiling of uterine tissues identified 403 genes reversed by YZOL treatment, including 280 upregulated and 123 downregulated genes in the YZOL-H versus PD comparison. KEGG pathway enrichment analysis indicated that these reversed genes were primarily involved in the TGF-β, Rap1, PI3K-Akt, and MAPK signaling pathways, as well as ovarian steroidogenesis. Functional annotation further revealed that these pathways are closely associated with nociceptive signaling, inflammatory responses, synaptic activity, and hormone biosynthesis, and that their aberrant activation contributes to pain sensitization, inflammatory mediator release, and excessive uterine smooth muscle contraction during PD progression. Integrative analysis combining transcriptomics and network pharmacology identified seven core targets associated with key pathological processes, including pain transmission, inflammatory regulation, and uterine smooth muscle contraction. Molecular docking analysis using AutoDock Vina demonstrated that berberine, peucedanoside, bakuchiol alcohol, and other constituents exhibited strong binding affinities toward these targets, with binding energies comparable to or exceeding those of positive control compounds. In addition, several compounds showed favorable oral bioavailability, suggesting their potential contribution to the in vivo efficacy of YZOL. Based on bioinformatics analysis and batch molecular docking, a multidimensional "active component-key target-biological effect" network was constructed to systematically illustrate the therapeutic mechanism of YZOL against PD. Collectively, these findings indicate that YZOL exerts anti-dysmenorrheic effects through a multi-component, multi-target, and multi-pathway mode of action, in which key constituents including berberine, peucedanoside, bakuchiol alcohol, dihydrochelerythrine, and imperatorin may act on targets such as IL1B, PRKCG, TRPV1, and PTGER2 to coordinately modulate pain signaling, inflammatory responses, and uterine smooth muscle contraction. The experiment was approved by the Laboratory Animal Ethics Committee of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (approval No. 2021B020).

This study focuses on the innovative applications of microneedles in transdermal drug delivery, aiming to explore their underlying mechanisms for overcoming skin barrier limitations and summarise cutting-edge advances. Recent transdermal delivery research has increasingly emphasised mechanism optimisation and material innovation for microneedles. This review analyses five delivery mechanisms — including "poke and patch" and "coat and poke" — clarifying their principles, advantages, and existing challenges. By examining application cases across ophthalmic disorders, dermatology, oncology, autoimmune diseases, and chronic metabolic conditions, it demonstrates broad prospects for drug delivery efficiency and health monitoring. Future efforts must address critical challenges including scalable production, long-term safety validation, and personalised treatment approaches to accelerate clinical translation.

This study aimed to investigate the hepatoprotective effects of the combination of berberine (BBR) and stachyose (Sta) in spontaneous type 2 diabetic KKAy mice. KKAy mice were randomly divided into four groups (n = 14 per group): Model control (model), stachyose (Sta, 200 mg·kg^-1), berberine (BBR, 100 mg·kg^-1), and BBR + Sta (100 mg·kg^-1 BBR + 200 mg·kg^-1 Sta), with oral gavage of water, Sta, BBR, and BBR + Sta respectively for eight weeks. At the end of the experiment, serum and liver tissues were collected, the liver weight was measured, and liver index was calculated. Lipid content and oxidative stress-related indicators in liver were measured. Meanwhile, the levels of lipid, transaminase, and oxidative stress in serum were determined. The expression levels of genes related to lipid metabolism and inflammation in the hepatic tissues were detected using qPCR. The number of macrophages in the liver tissues was measured by flow cytometry. Our findings revealed that the combination of BBR and Sta significantly reduced the liver index, decreased hepatic contents of triglyceride (TG), total cholesterol (TC), nitric oxide (NO), inducible nitric oxide synthase (iNOS), and malonaldehyde (MDA), improved liver histomorphology, attenuated lipid deposition, lowered serum lipids and alanine aminotransferase (ALT) levels, and suppressed the expression of lipid synthesis-related genes [fatty acid synthetase (Fasn), sterol regulatory element-binding protein 1c (Srebp1c)] and inflammation-related genes [interleukin-6 (Il-6), tumor necrosis factor-α (Tnf-α), monocyte chemoattractant protein-1 (Mcp-1)] in hepatic tissues. Furthermore, the combination treatment reduced the total number of hepatic macrophages (CD11b⁺F4/80⁺) and M1 macrophages (F4/80⁺CD11c⁺), and attenuated the antigen-presenting capacity of macrophages. Notably, BBR combined with Sta was superior to BBR alone in reducing blood lipids and inhibiting the expression of hepatic pro-inflammatory genes Il-6. However, no significant difference was observed between the two groups in alleviating hepatic macrophage infiltration and improving oxidative stress indicators. Collectively, the combination of BBR and Sta exerts anti-MASLD (metabolic dysfunction-associated steatotic liver disease) effects by ameliorating hepatic lipid accumulation, inflammation, and oxidative stress, as well as reducing macrophage number and weakening its function. Furthermore, the effects of the combination in improving MASLD are better than BBR alone. These findings suggest that BBR combined with Sta is a potential effective strategy for the treatment of MASLD. The animal experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College.

Bile acids (BAs) have evolved from their traditional role as auxiliary molecules in lipid digestion to critical signaling molecules regulating host metabolism. In recent years, the role of microbiota-derived bile acid-modifying enzymes and their mediated novel bile acid metabolic pathways in the pathogenesis and progression of metabolic diseases has become increasingly prominent. These microbial enzymes fine-tune glucose and lipid metabolism, energy homeostasis, and inflammatory responses by modulating the composition and proportion of the bile acid pool, thereby influencing the activity of key receptors such as the farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor (TGR5). The theory of "harmonizing the liver and spleen" in traditional Chinese medicine (TCM) is closely related to the maintenance of homeostasis of the liver-spleen axis. TCM posits that "liver Qi failing to ensure free flow" (liver dysfunction) and "spleen failing to transport and transform" (spleen dysfunction) are the core pathogenesis of metabolic diseases, while modern research has confirmed their intrinsic pathophysiological links to bile acid metabolic disorders and gut microbiota dysbiosis. Studies have shown that TCM formulations and active ingredients based on the "harmonizing the liver and spleen" principle can effectively ameliorate metabolic disorders such as insulin resistance and lipid accumulation by targeted intervention of microbiota-derived bile acid-modifying enzymes, regulating downstream receptor signaling pathways like FXR and TGR5, consequently correcting bile acid metabolic abnormalities and remodeling the gut microbiota structure. This review systematically summarizes the key targets of the microbiota-derived bile acid-receptor axis in metabolic diseases and delves into the intervention mechanisms of "harmonizing the liver and spleen" TCM strategies based on this axis, aiming to provide a new scientific explanation and potential therapeutic strategies for the prevention and treatment of metabolic diseases with TCM.

In 2025, innovation in drug development remained stable, with the proportion of first-in-class drugs continuing to increase. The Center for Drug Evaluation and Research (CDER) of the US Food and Drug Administration (FDA) approved a total of 46 new drugs in the past year, including 34 new molecular entities (NMEs) and 12 biologics license applications (BLAs). The number of approvals slightly decreased compared to the previous three years. This year, 31 small molecule drugs were approved, accounting for 67% of the total, among which 13 were first in class small molecule drugs. The treatment areas covered rare diseases, oncology, autoimmune diseases, respiratory diseases, and more. Several first in class small molecule drugs have breakthrough clinical value, such as the world's first non-opioid analgesic drug, NaV1.8 inhibitor suzetrigine, the first approved local TRPM8 receptor agonist acoltremon for dry eye disease, the first targeted mitochondrial inner membrane cardiolipin elamipretide, the first approved selective phosphodiesterase 4B (PDE4B) inhibitor nerandomilast for idiopathic pulmonary fibrosis (IPF), and the first selective oral Menin-MLL inhibitor iftomenib. First in class drugs have significant clinical, academic, and commercial value and have attracted extensive attention from patients, researchers and enterprises. This article briefly analyzes the research background, process and therapeutic applications of three representative first in class small molecule drugs from the perspective of medicinal chemistry, with the aim of providing more research directions and methods for the development of first in class drugs.

Deciphering the "multi-component, multi-target" synergistic regulation of traditional Chinese medicine (TCM) is a pivotal scientific challenge, particularly given ongoing debates over its relevance to holistic therapeutic outcomes and disease prognosis. Building on the framework of Molecular Holistic State Medicine and the concept that mesoscale key functional modules, termed functional assemblies, serve as the structural basis for TCM's holistic efficacy, this study employs "Xiaoke", a condition where TCM demonstrates recognized therapeutic advantages, and the classical formula Xiaoke Prescription as a proof-of-concept model. Guided by the translational principle of "from clinical observation, through experimental validation, back to clinical confirmation", the investigation starts with a retrospective matched clinical cohort to characterize the molecular holistic profile of diabetes and its evolution under Xiaoke Prescription treatment. These clinical findings are then integrated with mechanistic studies to identify the mesoscale key functional modules responsible for Xiaoke Prescription's antidiabetic effects and to reveal the nonlinear regulatory dynamics through which multiple bioactive components modulate multiple targets within these modules. Finally, prospective clinical trials are conducted to verify the synergistic antidiabetic mechanisms of Xiaoke Prescription through the holistic response of the identified mesoscale modules. By shifting mechanistic interpretation from "macroscopic phenotypes" and "microscopic molecules" to "systems-level integration", this study proposes a novel paradigm and technical platform for unraveling the "multi-component, multi-target" synergistic mechanisms underlying TCM interventions.

Schisandra chinensis, a traditional Chinese materia medica, possesses unique pharmacological activities and extensive clinical application value. Its processing techniques have evolved and improved over thousands of years. In the traditional Chinese medicine system, the processing of Schisandra chinensis directly affects its efficacy and is closely related to quality control and medication safety. Currently, there are still deficiencies in the standardization of processing techniques, quality control of active components, and research on the component-efficacy relationship. This review summarizes the historical evolution and modern technological advancements in the processing of Schisandra chinensis. Integrating contemporary analytical techniques and pharmacological studies, it discusses the quality control methods for its main active components, the mechanisms by which different processing methods influence these components and their efficacy, as well as its applications in metabolic diseases, liver diseases, respiratory diseases, and neurological disorders. This paper aims to provide a reference for the standardization of processing techniques, the precision of quality control, and the modernization of clinical applications of Schisandra chinensis.

Microreactors and related technologies, as key components of continuous manufacturing, offer significant advantages in pharmaceutical production, including enhanced manufacturing flexibility, substantial cost reduction, shortened reaction times, improved production efficiency, environmental sustainability, and strengthened supply chain resilience. They are widely regarded as a core enabling technology for realizing continuous pharmaceutical manufacturing and driving the transformation and upgrading of the pharmaceutical industry. In particular, the integration of microreactors with artificial intelligence and automation technologies has reshaped the traditional large-scale production paradigm of "reactor-production line-manufacturing plant", giving rise to new characteristics such as intelligent controllability, operational flexibility, and mobility, as well as modular and stepwise integration, and on-demand production. This paper systematically reviews the performance characteristics of various types of microreactors in pharmaceutical synthesis and their potential applications in intelligent, continuous pharmaceutical manufacturing. Furthermore, it analyzes the development of intelligent and distributed pharmaceutical synthesis systems enabled by the deep integration of artificial intelligence and chip-based microreactors, aiming to achieve continuous, precise, and emergency-responsive drug production, thereby providing important support for the digitalization and intelligent transformation of pharmaceutical manufacturing.

Halorotetin B is a natural terpenoid compound isolated from the tunic of Halocynthia roretzi. Studies have shown that this compound exhibits significant anti-tumor activity. However, its anti-inflammatory potential remains unexplored, likely owing to the multi-target nature of natural compounds. In this study, we investigated the anti-inflammatory activity of Ha. B. The results showed that Ha. B significantly inhibited the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Mechanistically, network pharmacology analysis and Western blot assays verified that Ha. B exerts its anti-inflammatory function by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Finally, natural product target prediction revealed that Ha. B may directly target mouse double minute 2 (MDM2). Cellular thermal shift assay (CETSA) results confirmed that Ha. B could interact with MDM2 in cells, and molecular docking was performed to simulate their physical binding mode. Meanwhile, RNA interference experiments further verified that Ha. B exerts its anti-inflammatory activity through binding to the E3 ubiquitin ligase MDM2.

The 2025 edition of the Chinese Pharmacopoeia defines films as film-like preparations made by processing active pharmaceutical ingredients with suitable polymers, intended for oral or mucosal use. Among these, orodispersible films (ODFs) are specifically defined as films that rapidly dissolve in the oral cavity to exert systemic or local effects. ODFs circumvent the drawbacks associated with orally disintegrating tablets, such as fragility and the potential risk of choking. This dosage form has aroused significant interest among both academic world and the pharmaceutical industry due to its accurate dosing, portability, and suitability for elderly and pediatric patients or those with swallowing difficulties. This review summarizes the advantages and limitations of ODFs, their listing status, suitable active pharmaceutical ingredients, commonly used excipients, preparation techniques, and emerging nanoparticle technologies. Additionally, it emphasizes quality evaluation requirements—such as dissolution, disintegration time, and mechanical properties—tailored to the characteristics of this dosage form. The aim is to provide readers and researchers with a comprehensive understanding of the development and evaluation of ODFs.